The present invention relates to a novel method for the preparation of a .beta.-thiolactam compound. More particularly, the present invention relates to a simple and efficient method for the preparation of a .beta.-thiolactam compound using readily available starting materials, which compound has usefulness as an intermediate in the synthesis of certain antibiotics having a chemical structure akin to that of penicillin or as a physiologically active substance.
.beta.-Thiolactam compound has a chemical structure akin to that of .beta.-lactam compounds contained in the principal skeletal structure of a large number of antibiotics including penicillin as a typical example so that .beta.-thiolactam compounds are expected, like .beta.-lactam compounds, to play a core role in physiologically active agents.
In fact, it is known that .beta.-thiolactam compounds having chemical structures resembling that of penicillin have antimicrobial activity according to the report appearing, for example, in Journal of the American Chemical Society, volume 97, page 5628 (1975). It is also known that some .beta.-thiolactam compounds have a sedative or anticonvulsive activity. See, for example, South African Patent No. 6707,088; Chem. Abstr. volume 70, 57602x (1969).
As a method for the synthetic preparation of a .beta.-thiolactam compound, a method generally applicable involves a reaction of a .beta.-lactam compound corresponding to the desired .beta.-thiolactam compound with phosphorus pentasulfide, boron sulfide or Lawesson reagent, i.e. (p-methoxyphenyl)thionophosphine sulfide dimer. See, for example, Chemische Berichte, volume 118, page 653 (1985). As a method for the formation of a .beta.-thiolactam ring, a method is disclosed in Chemische Berichte, volume 109, page 906 (1976), according to which a thioketene compound and a Schiff base are subjected to a [2+2] addition cyclization reaction.
These methods, however, do not provide a means for the direct formation of a .beta.-thiolactam compound having a structure resulting from condensation of a furan ring. If it ever be possible to accomplish such a structure, many problems to be solved remain unsolved for industrialization including low availability of the starting materials and complexity of the process involving a number of steps.
With an object to provide a simple and efficient method for the synthetic preparation of a .beta.-thiolactam compound capable of solving the above described problems in the prior art methods, the inventors have continued extensive investigations on .beta.-lactam compounds having correlation with .beta.-thiolactam compounds and previously discovered that a novel .beta.-lactam compound can be prepared in a high yield by the reaction of 2,3-dihydrofuran and an isocyanate ester compound and that a monocyclic .beta.-lactam compound can be obtained by the reaction of an alkyl vinyl ether and an isocyanate ester compound.